Genetic insights: High germline variant rate in an indigenous African cohort with early-onset colorectal cancer

IntroductionThe increase in incidence of colorectal cancer in young patients of African ancestry coupled with increased aggressiveness has warranted investigation of the heritable nature of these cancers. Only a limited number of published reports of hereditary colorectal cancer in indigenous African populations have been reported and no systematic screening of these groups has been performed previously. We aimed to investigate causative germline variants and to establish the incidence of pathogenic/likely pathogenic germline variants in the known colorectal cancer genes in indigenous African colorectal cancer patients using a next-generation sequencing (NGS) multigene panel.Materials and methodsPatients were selected from two hospitals in Cape Town and Johannesburg, South Africa. Patients with unresolved molecular diagnosis with an age of onset below or at 60 years were selected. Germline DNA samples were analyzed using a 14-gene NGS panel on the Ion Torrent platform. Variant calling and annotation were performed, and variants were classified according to the American College of Medical Genetics and Genomics guidelines. Observed variants were verified by Sanger sequencing and/or long-range PCR.ResultsOut of 107 patients, 25 (23.4%) presented with a pathogenic/likely pathogenic germline variant (PGV). Fourteen PGVs in at least one mismatch repair (MMR) gene were identified and verified in 12 patients (11.2%). Of these MMR gene variants, five were novel. The remaining 10 PGVs were in the APC, BMPR1A, MUTYH, POLD1, and TP53 genes.ConclusionThe high incidence of PGVs associated with early-onset colorectal cancer in indigenous African patients has important implications for hereditary colorectal cancer risk management. These findings pave the way for personalized genetic screening programs and cascade testing in South Africa. The next step would involve further screening of the unresolved cases using tools to detect copy number variation, methylation, and whole exome sequencing

Forschungsstudie: Alterssicherung von Personen mit Migrationshintergrund; Endbericht zum Auftrag des BMAS, Projektgruppe "Soziale Sicherheit und Migration" vom 02.01.2009

Aufgrund der demographischen Entwicklung und unter Annahme weitgehend stabiler Remigrationsmuster ist ein Anstieg des Bevölkerungsanteils älterer Menschen mit Migrationshintergrund zu erwarten. Viele der derzeit in Deutschland lebenden Migranten werden daher ihren Lebensabend hier verbringen. Ziel dieser Studie ist die vergleichende Darstellung der sozioökonomischen Lage der Migrantenpopulation und der autochthonen Bevölkerung. Dabei wird die Lebenslage von Personen im Rentenalter und von älteren Erwerbspersonen ab 45 Jahren vor dem Hintergrund ihrer spezifischen Bildungs- und Erwerbsverläufe untersucht. Damit wird eine belastbare empirische Grundlage für Handlungsempfehlungen zur Verbesserung der sozialen Lage von Frauen und Männern mit Migrationshintergrund im Alter geliefert

Inklusion!? Was ist daran wahr?

Das zentrale Anliegen dieses Betrages ist nicht, der Frage nachzugehen, was an Inklusion falsch ist, sondern, was an ihr wahr ist. Mit „wahr“ meine ich in Anlehnung an Stuart Hall nicht ein für allgemein gültig erklärbares Gesetz, das „wie ein Gesetz des Universums“ funktionieren kann, sondern eine Wahrheit, die „einleuchtend“ ist (Hall 1989, S. 189). D.h. sofern mit Inklusion ein Allgemeinheits- und Absolutheitsanspruch implizit oder explizit zum Ausdruck gebracht wird, führt dies tendenziell dazu, dass kritische Reflexionen verunmöglicht werden (vgl. Ahrbeck 2012, S. 46). Diese Tendenz der Universalisierung verweist auf herrschaftsstabilisierende Denkmuster im Diskurs, die eine Wahrheit beanspruchen und alternative Sichtweisen damit eher ausschließen. (DIPF/Orig.

An Investigation of Hearing (250-20,000 Hz) in Children with Endocrine Diseases and Evaluation of Tinnitus and Vertigo Symptoms

Introduction Despite much advancement in medicine, endocrine and metabolic diseases remain an important cause of morbidity and even mortality in children. Objective The present study was planned to investigate the evaluation of hearing that also includes high frequencies, and the presence and degree of vertigo and tinnitus symptoms in pediatric patients diagnosed with endocrine diseases such as type 1 diabetes mellitus (DM), growth hormone deficiency (GHD), obesity, idiopathic short stature, and precocious puberty Methods The present study included a patient group of 207 children patients diagnosed with endocrine disease (95 males, 112 females; mean age 9.71 years old [range 6-16 years old]) and a control group including 55 healthy children who do not have any kind of chronic disease (26 males, 29 females; mean age 9.33 years old [range 6-16 years old]). The subjects underwent a hearing test with frequencies between 250 and 20,000 Hz. The vestibular and tinnitus symptoms were evaluated with the Pediatric Vestibular Symptom Questionnaire. Results Out of 207 patients in the patient group, 5 (2.4%) had hearing loss in pure tones, 10 (4.8%) had it in high frequencies, 40 (19.3%) had tinnitus symptoms, and 18 (8.7%) had vertigo symptoms. A total of 4 out of 207 patients in the study group (1.9%), 2 out of 59 with type 1 DM patients (3.4%), 1 out of 46 with GHD (2.2%), and 1 out of 43 obesity patients (2.3%) had hearing loss, vertigo, and tinnitus symptoms. Conclusions Our results suggest that some childhood endocrine diseases can cause some changes in the inner ear, although the exact cause is unknown. Perhaps, a detailed hearing and balance examination should be a routine in a child diagnosed with an endocrine disease. We think it is necessary to work on more comprehensive patient groups and tests in the future

Association Between Endocrine Diseases and Serous Otitis Media in Children

Objective: Otitis media with effusion (OME) is a condition in which fluid is retained in the middle ear cavity. The association between endocrine disorders and OME has not yet been determined. This study aimed to investigate the presence of OME in children diagnosed with an endocrine disease and the relationship between these two conditions

Characterization of Class 1 and Class 2 lntegron Gene Cassettes in Escherichia coil Strains Isolated From Urine Cultures: A Multicenter Study

Ay Altintop, Yasemin/0000-0002-6586-5561WOS: 000378184000001PubMed: 27175490Escherichia coli is the most common pathogen isolated from both nosocomial and community acquired urinary tract infections. Although there are many studies from different centers concerning the antibiotic susceptibility of E.coli isolates in Turkey, the studies are quite few about class 1 and class 2 integron cassettes in clinical E.coli isolates from urinary samples. the aim of the study was to investigate the antibiotic susceptibility and the carriage of integron gene cassettes in E.coli strains isolated from urinary samples. A total of 626 E.coli strains isolated from urine cultures in microbiology laboratories located at 10 provinces from different regions of Turkey (Denizli, Ankara, Kayseri, Nigde, Sanliurfa, Kahramanmaras, Tokat, Malatya, Konya and Trabzon) between June 2011-June 2012 were included in the study. the identification and antibiotic susceptibility testing of the isolates were studied by conventional methods as well as Vitek (R) 2 Compact (bioMerieux, France) and BD Phoenix (TM) 100 (Becton Dickinson, USA) systems. the antibiotic susceptibilities of all the isolates were retested by Kirby-Bauer disk diffusion method according to CLSI recommendations in the main center of the study in order to achive the standardization. the presence of integrons was detected with polymerase chain reaction (PCR) method by using specific primers targeting class 1 (intl1) and class 2 (intl2) integrase gene regions. After integron amplification the samples were cloned and subjected to DNA sequencing. When the antibiotic susceptibility of the isolates were evaluated, the highest resistance was observed against most commonly used empirical antibiotics namely ampicillin and trimethoprim-sulfamethoxazole (SXT) with the mean rate of 58.6% (range: 43.8%-73.2%) and 41.2% (range: 35.4%-45.8%), respectively. the most effective antibiotics detected against the isolates were imipenem and amikacin with the lowest resistance rates of 0.2% (range: 0%-1.1%) and 0.6% (range: 0%-3.2%), respectively. the frequency of positive Intl1 gene and class 1 integron gene cassettes were found as 25.8% (162/626) and 16.6% (104/626), respectively, whereas the frequency of positive intl2 gene II and class 2 integron gene cassettes were 5.1% (32/626) and 3% (19/626), respectively. the lowest intl1 gene frequency was detected in the isolates from Kayseri (16.6%) and the highest in the isolates from Kahramanmaras (35.4%) provinces. While there was no intl2 gene in the isolates from Denizli and Kayseri, the highest frequency was 12.1% in the isolates from Sanliurfa province. dfrA1 gene, the most frequent gene among integron gene cassettes was positive in 31 class 1 integron gene cassette alone, and positive with aadA1 gene in 18 class 1 integron gene cassettes. dfrA1 gene was positive with aadA1 a just in one isolate. dfrA17 allele was positive in one isolate alone, in 28 isolates with aadA1, and in 15 isolates with aadA5. aadA1 gene was detected in four isolates. dfrA17-sat-aadA5 co-existence was detected among class 2 integron gene cassette in isolates from six provinces. dfrA1-sat-aadA1 was detected in one isolate from Ankara province and dfrA1 was detected in one isolate in Nigde province only. As a result, dfrA1 and aadA1 genes are the most common types of genes among class 1 and class 2 integron gene cassettes in E.coli isolated from urine cultures. It was concluded that high resistance against streptomycin (31.2%) and SXT (41.2%) supported the dissemination of integron-mediated genes dfr, sul1 and aad in the isolates